A5082722198- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Tryptophan and brain disorders
- Cholinesterase and Neurodegenerative Diseases
- Neurological disorders and treatments
- Parkinson's Disease Mechanisms and Treatments
- Functional Brain Connectivity Studies
- Schizophrenia research and treatment
- Pain Mechanisms and Treatments
- Bipolar Disorder and Treatment
- Neuroscience and Music Perception
- Medical Imaging Techniques and Applications
- Computational Drug Discovery Methods
- Action Observation and Synchronization
- Stress Responses and Cortisol
- Nicotinic Acetylcholine Receptors Study
- Adenosine and Purinergic Signaling
- Botulinum Toxin and Related Neurological Disorders
- Advanced Neuroimaging Techniques and Applications
- Memory and Neural Mechanisms
- Pediatric Pain Management Techniques
- Mental Health and Psychiatry
- Restless Legs Syndrome Research
- Infant Development and Preterm Care
- Motor Control and Adaptation
Janssen (Belgium)
2015-2024
Johnson & Johnson (United Kingdom)
2024
University of Antwerp
2008-2023
Hertie Institute for Clinical Brain Research
2020
German Center for Neurodegenerative Diseases
2020
Janssen (United States)
2020
Boston Children's Hospital
2012
β-Secretase enzyme (BACE) inhibition has been proposed as a priority treatment mechanism for Alzheimer's disease (AD), but initiation may need to be very early. We present proof of atabecestat (also known JNJ-54861911), an oral BACE inhibitor the AD, in Caucasian and Japanese populations with early AD who do not show signs dementia.In two similarly designed phase I studies, sample amyloid-positive elderly patients comprising 45 diagnosed preclinical (n = 15, Clinical Dementia Rating [CDR] 0)...
Background: Overlapping cerebrospinal fluid biomarkers (CSF) levels between Alzheimer's disease (AD) and non-AD patients decrease differential diagnostic accuracy of the AD core CSF biomarkers. Amyloid-β (Aβ) isoforms might improve versus non-
Abstract Background Atabecestat, a potent brain-penetrable inhibitor of BACE1 activity that reduces CSF amyloid beta (Aβ), was developed for oral treatment Alzheimer’s disease (AD). The long-term safety and effect atabecestat on cognitive performance in participants with predementia AD two phase 2 studies were assessed. Methods In the placebo-controlled double-blind parent ALZ2002 study, aged 50 to 85 years randomized (1:1:1) placebo or 10 mg once daily (later reduced 5 25 mg) 6 months....
• In older healthy subjects, FA and MD show overall good test-retest reliability & reproducibility. is sistematically more reproducible than across the entire brain anatomy. reliable in subcortical white matter regions. high low reproducibility regions, variability between subjects statistical power low. high.
Accumulation of amyloid β peptides (Aβ) is thought to be one the causal factors Alzheimer’s disease (AD). The aspartyl protease β-site precursor protein cleaving enzyme 1 (BACE1) rate-limiting for Aβ production, and therefore, BACE1 inhibition a promising therapeutic approach treatment AD. Starting with dihydro-1,3-thiazine-based lead, Compound J, we discovered atabecestat (JNJ-54861911) as centrally efficacious inhibitor that was advanced into EARLY Phase 2b/3 clinical trial preclinical AD...
Abstract Objectives Safety, tolerability, pharmacokinetics, and pharmacodynamics of a novel β‐site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor, JNJ‐54861911, were assessed after single multiple dosing in healthy participants. Methods Two randomized, placebo‐controlled, double‐blind studies performed using ascending JNJ‐54861911 doses (up to 14 days) young elderly Regular blood samples frequent CSF samples, up 36 hours last dose, collected assess the pharmacokinetic...
Abstract This study compared the bioavailability of two candidate fixed‐dose combinations (FDCs: G003 and G004) darunavir/cobicistat 800/150 mg with that darunavir 800 ritonavir 100 coadministered as single agents. Short‐term safety tolerability FDC formulations were also assessed. open‐label trial included 36 healthy volunteers assessed steady‐state pharmacokinetics over 3 randomized, 10‐day treatment sequences, under fed conditions. Blood samples for determination plasma concentrations...
Background: Central nervous system-derived interleukin-1β plays a role in mood disorders. P2X7 receptor activation by adenosine-triphosphate leads to the release of interleukin-1β. Aims: This first-in-human study evaluated safety, tolerability, pharmacokinetics and pharmacodynamics novel central system-penetrant antagonist, JNJ-54175446, healthy participants. Methods: The had three parts: an ascending-dose fasted participants (0.5–300 mg JNJ-54175446); fed (50–600 mg); cerebrospinal fluid...
Activated microglia express the translocator protein (TSPO) on outer mitochondrial membrane. <sup>18</sup>F-PBR111 is a second-generation PET ligand that specifically binds TSPO, allowing in vivo visualization and quantification of neuroinflammation. The aim this study was to evaluate whether test–retest variability healthy controls acceptable detect psychosis-associated neuroinflammatory signal schizophrenia. <b>Methods:</b> Dynamic 90-min scans were obtained 17 male (HCs) 11 schizophrenia...
Background: This is the first report of pharmacodynamic (PD) effects selective, potent and brain-penetrant P2X7 receptor (P2X7R) antagonist JNJ-54175446. Activation P2X7R, an adenosine triphosphate-gated ion channel, leads to production pro-inflammatory cytokines, which have been linked neuroinflammation play a role in pathogenesis mood disorders. Previous clinical studies with JNJ-54175446 demonstrated peripheral target engagement by assessing ex vivo lipopolysaccharide (LPS)-stimulated...
Objective: Different patterns of immune system upregulation are present in the acute versus post-treatment states psychotic illness. We explored existence state and trait markers peripheral two immune-associated neuroendocrine pathways (IDO GTP-CH1 pathway) a longitudinal sample psychosis patients. also evaluated association these with neuropsychiatric symptomatology. Method: Plasma concentrations blood were measured transdiagnostic group 49 inpatients 52 matched healthy control subjects....
• The cholinergic system is important for different central nervous functions, including memory, learning and attention. Scopolamine, a centrally active muscarinic antagonist, has been used to model dementia demonstrate the pharmacological effects of drugs, but most concentration-effect relationships are unknown.• We determined pharmacokinetic-pharmacodynamic scopolamine using multidimensional test battery in large group healthy volunteers. results suggested there various functional systems...
In this study we explored the possibility of automating PGP9.5 immunofluorescence staining assay for diagnosis small fiber neuropathy using skin punch biopsies. The laboratory developed test (LDT) was subjected to a validation strategy as required by good practice guidelines and compared well-established gold standard method approved European Federation Neurological Societies (EFNS). To facilitate automation, use thinner sections. (16 µm) evaluated. Biopsies from previously published studies...
Normative cognitive data can help to distinguish pathological decline from normal aging. This study presents normative the Cambridge Neuropsychological Test Automated Battery, using linear regression and nonlinear quantile approaches.Heinz Nixdorf Recall participants completed Battery tests: paired-associate learning, spatial working memory, reaction time. Data were available for 1349-1529 healthy adults aged 57-84 years. Linear analyses examined age-related changes, adjusting sex education....
Background: A mild pro-inflammatory status accompanies bipolar disorder (BD). Inflammation can cause a shift in monoamine metabolism, thereby activating more cytotoxic pathways. The extent to which low-grade inflammation BD interacts with metabolism and how this accords aging clinical course is unknown. Objectives: We evaluated the presence of alterations throughout different mood states role therein. Methods: Sixty-seven patients were included during an acute episode, either depressive (n =...
Abstract Objectives Cytokines are thought to contribute the pathogenesis of psychiatric symptoms by kynurenine pathway activation. Kynurenine metabolites affect neurotransmission and can cause neurotoxicity. We measured inflammatory markers in patients with bipolar disorder (BD) studied their relation mood. Methods Patients BD suffering from an acute mood episode were assigned depressive (n = 35) or (hypo)manic 32) subgroup. Plasma levels [cytokines, C‐reactive protein] [tryptophan (TRP),...
The β-site amyloid-β protein precursor (AβPP) cleaving enzyme-1 (BACE1) is the rate limiting enzyme in generation of peptide (Aβ) from AβPP, one major pathways Alzheimer's disease (AD) pathology. Increased BACE1 levels and activity have been reported brain patients with sporadic AD. Therefore, changes cerebrospinal fluid (CSF) also investigated as a possible biomarker disease. We analyzed CSF elderly healthy participants before after chronic treatment BACE inhibitor (BACEi) evaluated...
Alzheimer's disease (AD) is characterized neuropathologically by extracellular amyloid beta (plaques) and intracellular hyperphosphorylated tau (neurofibrillary tangles). There evidence for prion-like spread of in AD, anti-tau antibodies are under clinical investigation modification binding to seeds the interstitial fluid (ISF). JNJ-63733657 a humanized IgG1 monoclonal antibody with high affinity phosphorylated (p217+). This depletes toxic species vitro seeding assays reduces vivo models. A...